Switching Off and Desensitization of 7-Helix Transmembrane Receptors

The best investigated is the desensitization of the adrenaline receptor type pi and of rhodopsin. Rhodopsin has the function of a light receptor in the process of vision. It 

Furthermore, Ser/Thr phosphorylation can be used as a switch for coupling a given receptor to different Ga subunits. Protein kinase A-mediated phosphorylation of the / -adrenergic receptor has been shown to switch coupling of the receptor from Gs to G, and initiate a new set of signalling events (Daaka et al., 1997). 

In addition, phosphorylation-mediated binding of arrestins to the receptor (see below) serves as a means to couple G protein-coupled receptor to another signaling pathway, the MAPK cascade. 

Two classes of protein kinases are mainly involved in the phosphorylation and desensitization (review Freedman and Lefkowitz, 1996)  

Phosphorylation of the cytoplasmic domain of 7-helix transmembrane receptors can take place via cAMP-dependent protein kinases protein kinase A) or via protein kinase C (Chapter 7) (Fig. 5.9). This is a feedback mechanism. The hormonal activation of the receptor leads, via G proteins and adenylyl cyclase/cAMP, to activation of protein kinases of type A (see Sections 5.6.1 and 6.1, and Chapter 7). The activated protein kinases phosphorylate the receptor in the region of the cytoplasmic domain on Ser/Thr residues. Regulation via adenylyl cyclase/cAMP/proteinkinase A is an example of a heterologous desensitization, since adenylyl cyclase can be activated by a variety of signals originating from different signaling pathways (see Section 5.6.1). 

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